Parkinson disease 13, autosomal dominant, susceptibility to

Summary

Parkinson disease 13, autosomal dominant, susceptibility to (MONDO:0012466) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 52

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Parkinson disease 13, autosomal dominant, susceptibility to
Mondo ID	MONDO:0012466
MeSH	C565204
OMIM	610297
UMLS	C1853202
MedGen	343992
Is cancer (heuristic)	no

Also known as: HTRA2 young-onset Parkinson disease · PARK13 · Parkinson disease 13 · Parkinson disease 13, autosomal dominant, susceptibility to · young-onset Parkinson disease caused by mutation in HTRA2

Data availability: 52 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › Parkinson disease 13, autosomal dominant, susceptibility to

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

52 retrieved; paginated sample, class counts are floors:

25 uncertain significance, 9 likely benign, 7 benign, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 1 risk factor, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3586941	NM_013247.5(HTRA2):c.420del (p.Ala141fs)	HTRA2	Likely pathogenic	criteria provided, single submitter
30583	NM_013247.5(HTRA2):c.427C>G (p.Pro143Ala)	HTRA2	risk factor	no assertion criteria provided
337133	NM_013247.5(HTRA2):c.825T>C (p.Val275=)	HTRA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337134	NM_013247.5(HTRA2):c.873T>C (p.Asn291=)	HTRA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337135	NM_013247.5(HTRA2):c.1046-13C>T	HTRA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337136	NM_013247.5(HTRA2):c.1131A>G (p.Leu377=)	HTRA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
895799	NM_013247.5(HTRA2):c.1056C>T (p.Ser352=)	HTRA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337120	NM_013247.4(HTRA2):c.-359G>A	AUP1	Uncertain significance	criteria provided, single submitter
337121	NM_013247.4(HTRA2):c.-314G>A	AUP1	Uncertain significance	criteria provided, single submitter
896013	NM_013247.4(HTRA2):c.-598G>A	AUP1	Uncertain significance	criteria provided, single submitter
896015	NM_013247.4(HTRA2):c.-361G>A	AUP1	Uncertain significance	criteria provided, single submitter
1385413	NM_013247.5(HTRA2):c.1294C>T (p.Arg432Ter)	HTRA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
337118	NM_181575.5(AUP1):c.25C>T (p.Pro9Ser)	HTRA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
337122	NM_013247.4(HTRA2):c.-236G>C	HTRA2	Uncertain significance	criteria provided, single submitter
337123	NM_013247.4(HTRA2):c.-216G>A	HTRA2	Uncertain significance	criteria provided, single submitter
337125	NM_013247.4(HTRA2):c.-136C>G	HTRA2	Uncertain significance	criteria provided, single submitter
337126	NM_013247.4(HTRA2):c.-86G>C	HTRA2	Uncertain significance	criteria provided, single submitter
337128	NM_013247.5(HTRA2):c.241G>A (p.Ala81Thr)	HTRA2	Uncertain significance	criteria provided, single submitter
337130	NM_013247.5(HTRA2):c.507-10T>A	HTRA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
337131	NM_013247.5(HTRA2):c.507-9C>A	HTRA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
337138	NM_013247.5(HTRA2):c.1346C>T (p.Thr449Ile)	HTRA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
337140	NM_013247.5(HTRA2):c.*249G>C	HTRA2	Uncertain significance	criteria provided, single submitter
337141	NM_013247.5(HTRA2):c.*291G>A	HTRA2	Uncertain significance	criteria provided, single submitter
337144	NM_013247.4(HTRA2):c.*513T>A	HTRA2	Uncertain significance	criteria provided, single submitter
3586942	NM_013247.5(HTRA2):c.508C>A (p.His170Asn)	HTRA2	Uncertain significance	criteria provided, single submitter
895797	NM_013247.5(HTRA2):c.937C>T (p.Leu313=)	HTRA2	Uncertain significance	criteria provided, single submitter
896083	NM_013247.5(HTRA2):c.1079G>A (p.Arg360His)	HTRA2	Uncertain significance	criteria provided, single submitter
896084	NM_013247.5(HTRA2):c.*265C>T	HTRA2	Uncertain significance	criteria provided, single submitter
897610	NM_013247.4(HTRA2):c.-136C>T	HTRA2	Uncertain significance	criteria provided, single submitter
897673	NM_013247.5(HTRA2):c.*267C>T	HTRA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LOXL3	Orphanet:250984	Autosomal recessive Stickler syndrome
HTRA2	Orphanet:2828	Young-onset Parkinson disease
HTRA2	Orphanet:505208	3-methylglutaconic aciduria type 8

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LOXL3	HGNC:13869	ENSG00000115318	P58215	Lysyl oxidase homolog 3	clinvar
HTRA2	HGNC:14348	ENSG00000115317	O43464	Serine protease HTRA2, mitochondrial	clinvar
AUP1	HGNC:891	ENSG00000115307	Q9Y679	Lipid droplet-regulating VLDL assembly factor AUP1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LOXL3	Lysyl oxidase homolog 3	Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins.
HTRA2	Serine protease HTRA2, mitochondrial	Serine protease that shows proteolytic activity against a non-specific substrate beta-casein.
AUP1	Lipid droplet-regulating VLDL assembly factor AUP1	Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	12.2×	0.239
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LOXL3	Enzyme (other)	yes	1.4.3.13	SRCR, Lysyl_oxidase, Lysyl_oxidase_CS
HTRA2	Protease	yes	3.4.21.108	PDZ, Peptidase_S1C, Peptidase_S1_PA
AUP1	Other/Unknown	no		CUE, AUP1_CUE

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
tendon of biceps brachii	1
tibia	1
cortical plate	1
right coronary artery	1
trabecular bone tissue	1
body of pancreas	1
granulocyte	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LOXL3	198	ubiquitous	marker	tibia, cartilage tissue, tendon of biceps brachii
HTRA2	280	ubiquitous	marker	cortical plate, right coronary artery, trabecular bone tissue
AUP1	287	ubiquitous	marker	granulocyte, body of pancreas, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HTRA2	4,023
AUP1	2,746
LOXL3	1,130

Intra-cohort edges

A	B	Sources
HTRA2	LOXL3	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HTRA2	O43464	13
AUP1	Q9Y679	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LOXL3	P58215	84.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial unfolded protein response (UPRmt)	1	200.3×	0.017	HTRA2
Crosslinking of collagen fibrils	1	190.3×	0.017	LOXL3
Collagen formation	1	152.3×	0.017	LOXL3
Elastic fibre formation	1	112.0×	0.018	LOXL3
Assembly of collagen fibrils and other multimeric structures	1	66.8×	0.024	LOXL3
Mitochondrial protein degradation	1	38.1×	0.035	HTRA2
Extracellular matrix organization	1	21.0×	0.053	LOXL3
Dengue Virus-Host Interactions	1	15.2×	0.064	AUP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pentacyclic triterpenoid metabolic process	1	5617.3×	0.005	HTRA2
negative regulation of type 2 mitophagy	1	2808.7×	0.005	HTRA2
fibronectin fibril organization	1	2808.7×	0.005	LOXL3
peptidyl-lysine oxidation	1	1872.4×	0.005	LOXL3
lipophagy	1	1872.4×	0.005	AUP1
protein localization to lipid droplet	1	1404.3×	0.006	AUP1
response to herbicide	1	1123.5×	0.006	HTRA2
regulation of autophagy of mitochondrion	1	936.2×	0.007	HTRA2
negative regulation of T-helper 17 cell lineage commitment	1	802.5×	0.007	LOXL3
mitochondrial protein catabolic process	1	510.7×	0.009	HTRA2
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	510.7×	0.009	HTRA2
programmed cell death	1	432.1×	0.009	HTRA2
positive regulation of integrin-mediated signaling pathway	1	432.1×	0.009	LOXL3
somite development	1	374.5×	0.009	LOXL3
retrograde protein transport, ER to cytosol	1	330.4×	0.009	AUP1
lipid droplet formation	1	330.4×	0.009	AUP1
lipid droplet organization	1	312.1×	0.009	AUP1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	312.1×	0.009	HTRA2
positive regulation of execution phase of apoptosis	1	280.9×	0.009	HTRA2
ceramide metabolic process	1	267.5×	0.009	HTRA2
execution phase of apoptosis	1	255.3×	0.009	HTRA2
protein autoprocessing	1	216.1×	0.010	HTRA2
regulation of multicellular organism growth	1	216.1×	0.010	HTRA2
cellular response to interferon-beta	1	175.5×	0.011	HTRA2
spinal cord development	1	170.2×	0.011	LOXL3
adult walking behavior	1	165.2×	0.011	HTRA2
obsolete positive regulation of protein targeting to mitochondrion	1	165.2×	0.011	HTRA2
forebrain development	1	117.0×	0.015	HTRA2
cellular response to heat	1	114.6×	0.015	HTRA2
intrinsic apoptotic signaling pathway in response to DNA damage	1	108.0×	0.015	HTRA2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
LOXL3	PYRITHIONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LOXL3	3	4
HTRA2	0	0
AUP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRITHIONE	4	LOXL3
DISULFIRAM	4	LOXL3
THIRAM	2	LOXL3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HTRA2	11	Binding:11
LOXL3	6	Binding:6
AUP1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LOXL3	1.4.3.13	protein-lysine 6-oxidase
HTRA2	3.4.21.108	HtrA2 peptidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

3 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PYRITHIONE	4	LOXL3
DISULFIRAM	4	LOXL3
THIRAM	2	LOXL3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	LOXL3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HTRA2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AUP1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HTRA2	11	—
AUP1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.